CPZ

protein-coding

carboxypeptidase Z, the group of M14 carboxypeptidases

Gene summary

This gene encodes a member of the metallocarboxypeptidase family. This enzyme displays carboxypeptidase activity towards substrates with basic C-terminal residues. It is most active at neutral pH and is inhibited by active site-directed inhibitors of metallocarboxypeptidases. Alternative splicing in the coding region results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001014447.3

Inheritance

—

ClinVar variants

P:1U:235B:43

Top phenotype

CPZ-related disorder

gnomAD constraint

pLI —, LoF o/e 1.7

Max pathogenic AF

—

Genomic locus

chr4:8,592,660-8,619,759

External References & Databases

Ensembl (ENSG00000109625)

Transcript & Mutation Effects

hg38 • Region Span ~27.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CPZ variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 235

CPZ-related disorderTotal: 35

not providedTotal: 20

Short statureTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001014447.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	10 clinvar	12 clinvar	23
missense		1 clinvar	228 clinvar	13 clinvar	7 clinvar	249
nonsense			2 clinvar	1 clinvar		3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	235	24	19	279

Highest pathogenic variant AF is 0.000020359632

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001014447.3	RefSeq	NP_001014447.2	11	MANE Select
ENST00000360986.9	Ensembl	ENSP00000354255.4	11	MANE Select
NM_001014448.3	RefSeq	NP_001014448.2	9	Standard
NM_003652.4	RefSeq	NP_003643.3	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
peptide metabolic process
Wnt signaling pathway
protein processing

Molecular Function

metallocarboxypeptidase activity
zinc ion binding

Cellular Component

extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360986
Coding exons: 11
Length: 27102
Individuals with no LoFs: 125030
Homozygous LoFs: 0
Heterozygous LoFs: 717
Defined: 125747
p: 0.00285

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-4.43	675	420	1.61	0.0000282	4151
Missense (PolyPhen)		283	176.33	1.6049		1740
Synonymous	-6.68	293	179	1.64	0.0000128	1292
Loss of Function	-3.26	43	25.3	1.70	0.00000117	290

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.0033	0.0033	notable
Ashkenazi Jewish	0.0056	0.0056	notable
East Asian	0.0060	0.0057	notable
Finnish	0.0035	0.0035	notable
European (Non-Finnish)	0.0022	0.0022	notable
South Asian	0.0026	0.0025	notable
Other	0.0036	0.0036	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cleaves substrates with C-terminal arginine residues. Probably modulates the Wnt signaling pathway, by cleaving some undefined protein. May play a role in cleavage during prohormone processing. {ECO:0000269|PubMed:11766880, ECO:0000269|PubMed:12417617, ECO:0000269|PubMed:9099699}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

RVIS EVS: -1.49
RVIS percentile EVS: 3.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.299

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium